The overall purpose of this research will be to define the mechanism by which growth hormone stimulates somatomedin production and how growth hormone and somatomedin interact with other hormones, growth factors, and non-hormonal factors to regulate somatic growth. We plan to determine the range of cell types which respond to growth hormone by the production of immunoreactive somatomedin-C and will determine the chemical nature of the immunoreactive somatomedin-C secreted into cell culture medium. We plan to determine whether the responsive cell types possess growth hormone receptors, and investigate whether in vitro cell culture conditions can be optimized to make this a more efficient source for the production of somatomedin-C. We wish to further define the range of growth factors and hormones in plasma in serum which together with somatomedin act as "progression factors" and investigate the cellular events stimulated by somatomedin-C which lead to DNA synthesis and cell replication. We will scale up the purification of somatomedin-C from Cohn Fraction IV of human plasma and use this material to raise additional antisera in rabbits and goats, complete the primary sequence analysis, and determine its in vivo effects in hypophysectomized animals.